Targeting Viruses Before They Enter the Body

Mymetics Seeks to Prevent Infection with Vaccines that Induce IgA Antibodies at the Mucosal Level

Mymetics’ HIV-1 preventive vaccine is based on gp41-derived antigens attached on the surface of virosomes that act as an antigen delivery system. Virosomes are nonreplicative vectors that are essentially spherical lipidic vesicles, representing reconstituted empty influenza virus envelopes harboring the hemagglutinine (HA) and neuraminidase (NA) viral proteins, devoid of the genetic material. The lipidated antigens (recombinant gp41 proteins on the left and P1 peptides on the right) are intercalated into the lipid membrane of virosomes through the lipid tail.

After more than 25 years of research, a vaccine to prevent AIDS remains elusive. A new vaccine being developed at Mymetics is drawing attention because of its unique approach. The vaccine provides both first-line mucosal and second-line cellular immunity, according to the company. It is designed to block early transmission of the virus at mucosal surfaces, preventing it from spreading throughout the body.

Called MYMV101, the vaccine combines a peptide that stimulates mucosal immunity with a modified gp41 antigen for additional cellular immunity. The antigens are delivered via virosomes, which are lipid membranes modeled after envelope viruses. These lipid-based carriers contain functional fusion viral proteins and rationally designed antigens. Virosomes fuse with target cells, but they do not replicate. The virosome platform was created at Berna Biotech and improved by Virosome Biologics, which Mymetics acquired in 2009.

The route of administration of MYMV101 is unusual, too. The vaccine is first injected intramuscularly then followed by an intranasal booster dose. This approach induces IgA antibodies at mucosal surfaces to block viral entry, as well as IgG antibodies circulating in the blood. “Our vaccine represents a first line of defense before the virus can settle in the tissues and spread within the body. Targeting a virus before it enters the body is probably more efficacious than after it invades the body and infects it,” says Jacques-Francois Martin, CEO.

Clues to IgA Protection

Mymetics researchers were inspired by observations that some men and women in Africa remain HIV-negative, despite being regularly exposed to HIV during unprotected sex. Morgane Bomsel, Ph.D., at INSERM in Paris, a key collaborator with Mymetics, discovered the reason for this natural resistance—the vaginal and rectal secretions of resistant individuals contain specific IgA antibodies. Dr. Bomsel showed that HIV enters human mucosal tissue by a transcytosis mechanism, and that IgA antibodies against a specific part of the gp41 protein could block this entry.

Most pathogens enter their hosts through mucosal surfaces, such as the respiratory, genito-urinary, or gastrointestinal tracts. They migrate in the bloodstream to organs where they replicate. Classic vaccines trigger mostly IgG antibodies in blood, but not IgA antibodies at the point of entry. Based on Dr. Bomsel’s results, researchers at Mymetics designed a vaccine formulation that induces IgA antibodies at the mucosal level. Most other HIV immunization projects have targeted IgG antibodies, or specific cytotoxic cells against HIV in the blood.

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